Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide and has a very poor prognosis. Its occurrence has been on the increase in recent years. Surgical resection and liver transplantation are the primary methods of treatment for HCC patients, but can only be applied to 15% of patients. The median survival time of unresectable or metastasizing HCC patients is only a few months. Existing systemic treatment methods are not effective for advanced HCC patients and a new method of treatment is needed for these patients. It has been established that the HCC occurs in multiple stages, however, the pathogenesis at a molecular level is not clear and many key factors are yet to be determined. In the past 30 years, it has become evident that the Ras/Raf/MEK/extracellular signal-regulated kinase (ERK) signaling pathway plays a significant role in the occurrence and development of HCC. This review focused on the association between the Ras/Raf/MEK/ERK signaling pathway and HCC.

Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor that functions to attenuate T cell activation. In this study, we knocked out (KO) PD-1 in cytotoxic T lymphocytes (CTLs) using CRISPR-Cas9 system to evaluate its effect on the anti-tumor activity of the CTLs against multiple myeloma (MM). Results show that PD-1 KO CTLs facilitate apoptosis and caspase activation of the co-cultured MM cells and enhanced MM cell death by 36% compared with the control. PD-1 KO also increased TNF-α and IFN-γ secretion of the CTLs by 2.4 and 1.9-fold respectively. The effectiveness of PD-1 KO in enhancing anti-tumor activity of the CTLs was verified in vivo using mouse xenograft model. The xenografted mice treated with PD-1 KO CTLs demonstrated repressed MM tumor growth and prolonged survival compared with the control group. We conclude that CRISPR-Cas9 is an efficient system to knock out PD-1 from CTLs and PD-1 KO could significantly enhance the anti-tumor activity of CTLs.

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◥Viral-based chimeric antigen receptor-engineered T (CAR T)cell manufacturing has potential safety risks and relatively high costs. The nonviral minicircle DNA (mcDNA) is safer for patients, cheaper to produce, and may be a more suitable technique to generate CAR T cells. In this study, we produced mcDNA-based CAR T cells specifically targeting prostate stem cell antigen (PSCA; mcDNA-PSCA-CAR T cells). Our results showed that mcDNA-PSCA-CAR T cells persisted in mouse peripheral blood as long as 28 days and demonstrated more CAR T-cell infiltration, higher cytokine secretion levels, and better antitumor effects. Together, our results suggest that mcDNA-CAR can be a safe and cost-effective platform to produce CAR T cells.

Colorectal cancer (CRC) is a common malignant tumor. 1 In recent decades, diagnosis and treatment technology has made great progress; the 5-year survival rate for CRC in the localized stage is now 90.1%. However, only 39% of CRC cases are detected in the localized stage, 2,3 and the 5-year survival rate in distant metastasis cases is 69.2%. Therefore, recent research has focused on the pathogenesis of CRC and more effective strategies for the early diagnosis and treatment of CRC. [4][5][6]

Aim: To produce dendritic cells (DCs) from CD34+ stem cells from cord blood and explore their prophylactic and curative effect against tumors by vaccinating humanized NSG mice. Materials & methods: Separated CD34+ stem cells from cord blood were cultured for 30 days, and the resultant DCs (CD34-DCs) were collected. The basic function of the CD34-DCs and the cytotoxicity of CD34-cytotoxic-T lymphocytes (CTLs) were tested in vitro, and tumor inhibition in a humanized NSG mouse tumor model was observed. Results: The number of CD34-DCs reached approximately 9 log. These cells performed functions similar to those of DCs derived from monocytes from peripheral blood (PBMC-DCs). The CTLs of the CD34-DCs (CD34-CTLs) presented a better antitumor effect in vitro. The obvious prophylactic and therapeutic antitumor effects of the CD34-DC vaccine were observed in the humanized NSG mouse models. Conclusion: CD34-DCs from cord blood were sufficient in quantity and quality as a vaccine agent against tumors in vitro and in vivo.

Atherosclerosis correlates with ischemic cardio-cerebrovascular diseases such as coronary heart disease. Long non-coding RNAs (lncRNAs) can promote atherosclerosis. We investigated the role of the lncRNA AK136714 in atherosclerosis. Compared with the healthy group, lncRNA AK136714 expression was elevated in the plaque and plasma of the atherosclerosis patients in a GEO dataset. AK136714 silencing inhibited atherosclerosis formation in ApoE-/- mice. AK136714 silencing also protected the endothelial barrier and inhibited endothelial cell inflammation. In vitro assays showed that knockdown of AK136714 suppressed the inflammatory response and apoptosis in human umbilical vein endothelial cells (HUVECs). Moreover, AK136714 was found to bind directly to HuR to increase the mRNA stability of TNF-α, IL-1β and IL-6 mRNAs. In addition, AK136714 promoted the transcription of Bim. This study expands our understanding of the role of lncRNA AK136714 in atherosclerosis and provides potential drug targets for the treatment of atherosclerosis.

The study focused on how to improve the diagnostic coincidence rate of patients with gallbladder stones and gallbladder cancer based on an optimized Segnet network algorithm and the relationship of gallbladder cancer with multiple tumor suppressor 1 (P16). 300 patients diagnosed with gallbladder cancer in the hospital were selected as the research subjects. The pyramid pooling operation was incorporated into the original Segnet network algorithm, and its performance was evaluated, factoring into the intersection of union (IoU), algorithm precision (Pre), and recall rate (Recall). After 8 hours of fasting, conventional ultrasound and contrast-enhanced ultrasound examinations were performed, and the images were evaluated by three experienced ultrasound diagnosticians. The positive signal of P16 immunohistochemical staining was brownish yellow, which was generally concentrated in the nucleus, and a small part was located in the cytoplasm. In each slice, ten visual fields were selected. Then, they were observed under a high-power mirror, and the number was counted. It was found that the optimized Segnet network algorithm increased the IoU by 7.3%, the precision by 8.2%, and the recall rate by 11.1%. The diagnostic coincidence rates of conventional ultrasound and contrast-enhanced ultrasound examinations for gallbladder cancer were 78.13% (25/32) and 87.5% (25/32), respectively. The positive expression rate of P16 in gallbladder adenocarcinoma (47.06%) was significantly lower than that of acute cholecystitis with gallbladder stones (84.38%) and gallbladder polyps (67.16%) ( P < 0.05 ). The positive expression rate of P16 in patients with stage III and stage IV (33.33% and 40%) was significantly lower than that in patients with stages I and II (87.5% and 80%) ( P < 0.05 ). The positive expression rate of P16 in high differentiation (86.67%) was significantly higher than that of moderate differentiation (40%) and poor differentiation (28.57%) ( P < 0.05 ). In short, contrast-enhanced ultrasound can effectively improve the diagnostic coincidence rate of gallbladder cancer, and the expression of P16 in gallbladder cancer is closely related to tumor staging and differentiation.